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Jennifer M. Noel, Wei Wang, Henry J. Kaplan, Doug C. Dean, Paul J. DeMarco, Maureen A. McCall; Effects of Granulocyte Colony Stimulation Factor in Mouse Models of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5463.
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Granulocyte Colony Stimulation Factor (G-CSF) is a glycoprotein, growth factor and cytokine produced by different tissues to stimulate the bone marrow to produce granulocytes and stem cells. We administered G-CSF to mice with toxin-induced or genetically-based retinal degeneration in vivo to examine its ability to target stem cells to the retina and ameliorate photoreceptor degeneration.
C57B6/J (B6) mice were injected intravenously with 20 or 25 mg/kg sodium iodate (NaIO3) to destroy retinal pigment epithelium (RPE). In experimental mice, subcutaneous injections of G-CSF were administered 4 hours after NaIO3 treatment and continued daily for 6 or 10 days (d). In rd10 mice with genetically-based photoreceptor degeneration, G-CSF was injected daily for 10 d beginning at post-natal day 15-17. Controls for each model received injections of vehicle only on the same schedules. ERG and OKR recordings were used in all experimental and control conditions to establish pretreatment baseline and post treatment effects of G-CSF. B6 mice were euthanized at 4 or 6 weeks post NaIO3 injection and rd10 mice at p30 or p45. Eyes were enucleated, fixed and processed for histology and immunohistochemistry.
Similar to the published literature, NaIO3 treatment leads to loss of retinal pigment epithelium and photoreceptors in the outer nuclear layer (ONL). This is accompanied by diminished ERG b-wave amplitudes and OKR responses. rd10 mice have already lost photoreceptors at P17 and their numbers decline further at p30. This is accompanied by significant declines in the ERG and OKR response. There was an increase in the number of cells in the ONL in G-CSF-treated mice in both the rd10 and NaIO3 models. This increase in cell number was not associated with restoration of the ERG in NaIO3-treated B6 mice, whereas the ERG was partially restored in rd10 mice. The OKR response was not restored in either retinal degeneration model.
Treatment with G-CSF leads to an increase in the number of cells in the ONL of the retina compared to control eyes in these two mouse models of retinal damage.
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